Addressing the Challenges of a Cross-National Investigation: Lessons from the Pittsburgh-Pisa Study of Treatment-Relevant Phenotypes of Unipolar Depression

17sireservedBackground: To date, no cross-national RCT has addressed the mechanisms underlying the relative success of pharmacological and psychotherapeutic interventions for depression. A multi-site clinical trial that includes psychotherapy as one of the treatments presents numerous challenges related to cross-site consistency and communication. Purpose: This report describes how those challenges were met in the study "Depression: The Search for Treatment Relevant Phenotypes", being carried out at the University of Pittsburgh and the University of Pisa, Italy. Methods: Implementing the study required the investigators to address methodological and practical challenges related to the different requirements of the two Institutional Review Boards (IRBs), psychotherapy training, independent evaluator training, patient recruitment, development of common tools for data entry, quality control and generation of weekly reports of patient progress as well as establishing a similar clinical and research framework in two countries with substantially different health care systems. Results: By having bilingual investigators and staff members who spent time at one another's sites, making use of frequent conference-call staff meetings and being flexible within the bounds of the sometimes contradictory requirements of the IRBs, the investigators were able to meet the human subjects protection requirements of both institutions, surmount language barriers to consistent therapist and evaluator training and develop common tools for study management. As a result, recruitment goals were met at both sites and retention rates were high. One instance of inconsistent implementation of the protocol was corrected within the first year. Limitations: This study was conducted in two Western cultures by researchers with long-standing collaboration. Our findings may not be generalizable to other countries or research settings. Conclusions: The implementation of a cross-national protocol and the adoption and maintenance of common procedures is possible when investigators are aware of the challenges this may present and are proactive in trying to address them. © Society for Clinical Trials 2008.mixedFRANK, E.; CASSANO, G.B.; RUCCI, P.; FAGIOLINI, A.; MAGGI, L.; KRAEMER, H.; KUPFER, D.J.; POLLOCK, B.; BIES, R.; NIMGAONKAR, V.; PILKONIS, P.; SHEAR, M.K.; THOMPSON, W.K.; GROCHOCINSKI, V.; SCOCCO, P.; BUTTENFIELD, J.; FORGIONE, R.N.Frank, E.; Cassano, G. B.; Rucci, P.; Fagiolini, A.; Maggi, L.; Kraemer, H.; Kupfer, D. J.; Pollock, B.; Bies, R.; Nimgaonkar, V.; Pilkonis, P.; Shear, M. K.; Thompson, W. K.; Grochocinski, V.; Scocco, P.; Buttenfield, J.; Forgione, R. N

Outcomes of Pediatric Patients with Therapy-Related Myeloid Neoplasms

Long-term outcomes after allogeneic hematopoietic cell transplantation (HCT) for therapy-related myeloid neoplasms (tMNs) are dismal. There are few multicenter studies defining prognostic factors in pediatric patients with tMNs. We have accumulated the largest cohort of pediatric patients who have undergone HCT for a tMN to perform a multivariate analysis defining factors predictive of long-term survival. Sixty-eight percent of the 401 patients underwent HCT using a myeloablative conditioning (MAC) regimen, but there were no statistically significant differences in the overall survival (OS), event-free survival (EFS), or cumulative incidence of relapse and non-relapse mortality based on the conditioning intensity. Among the recipients of MAC regimens, 38.4% of deaths were from treatment-related causes, especially acute graft versus host disease (GVHD) and end-organ failure, as compared to only 20.9% of deaths in the reduced-intensity conditioning (RIC) cohort. Exposure to total body irradiation (TBI) during conditioning and experiencing grade III/IV acute GVHD was associated with worse OS. In addition, a diagnosis of therapy-related myelodysplastic syndrome and having a structurally complex karyotype at tMN diagnosis were associated with worse EFS. Reduced-toxicity (but not reduced-intensity) regimens might help to decrease relapse while limiting mortality associated with TBI-based HCT conditioning in pediatric patients with tMNs